The interation of CAR-NK cell and tumor cells during the in vivo anti-tumor cell therapy

Chimeric antigen receptor (CAR) engineering of NK cells is an active area of research with early-phase clinical studies showing an excellent safety profile with encouraging clinical responses. However, the transcriptional signatures that control the fate of CAR-NK cell after infusion and their association with tumor control remain poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) to depict the evolution of various engineered CAR-NK cells from the ex vivo infusion products to the in vivo peak phase of tumor control and finally to the relapse phase. Single cell RNA sequencing (scRNA) has revolutionized high-thoughout systems-based analysis of cellular and functional heterogeneity, and dynamic changes in the immune response during the anti-tumor immune cell therapy . The goals of this work are to compare transcriptome profiling (RNA-seq) from both engrafted tumor cells and infused CAR-NK cells over time of treatment course to evaluate the kenetic of tumor cell response and effector functional change of CAR-NK cell. Our study represents the first detailed transcriptomic analysis of using CAR-NK cell therapy aganist Raji-engrafted mouse model. Collecting samples from different time points and organs, the data analysis reported here should privide an envision of the dynamic about how tumor response to immune cell therapy of using CAR-NK cells and also how immune effector fucntion of CAR-NK cell was modulated over time during the treatment courses. Overall design: The objective of this study was to investigate the kinetics of function and evolution of adoptively-transferred CAR-NK cells in the context of lymphoma treatment. Of particular interest to us was to determine the impact of IL-15 on the function and persistence of CAR-NK cell and to assess the contribution of IL-15 to NK-mediated anti-tumor activity. To accomplish this, we applied a multi-modal omics approach to characterize pre-infusion NK products and describe the evolution of NK cells post-infusion.